ACHROMYCIN V tetracycline hydrochloride is an antibiotic isolated from Streptomyces aureofaciens. Chemically it is the monohydrochloride of [4 -(4(alpha),4a(alpha),5a(alpha),6(beta),12a(alpha),)] -4- (Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3, 6, 10, 12, 12a-pentahydroxy-6-methyl-1, 11-dioxo-2-naphthacenecarboxamide.

ACHROMYCIN V oral dosage forms contain the following inactive ingredients:

Capsules: Blue 1, FD&C Yellow No. 6, Gelatin, Lactose, Magnesium Stearate, Red 28, Titanium Dioxide, Yellow 10 and other ingredients.

The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis. Tetracyclines are active against a wide range of gram-negative and gram-positive organisms.

The drugs in the tetracycline class have closely similar antimicrobial spectra, and cross-resistance among them is common.

Microorganisms may be considered susceptible if the MIC (minimum inhibitory concentration) is not more than 4 mcg/mL and intermediate if the MIC is 4 to 12.5 mcg/mL.

Susceptibility plate testing: A tetracycline disc may be used to determine microbial susceptibility to drugs in the tetracycline class. If the Kirby-Bauer method of disc susceptibility testing is used, a 30 mcg tetracycline HCl disc should give a zone of at least 19 mm when tested against a tetracycline-susceptible bacterial strain.

Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations and in a biologically active form.

INDICATIONS

ACHROMYCIN V is indicated in infections caused by the following microorganisms.

Rickettsiae:  (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, tick fevers).

Mycoplasma pneumoniae (PPLO, Eaton agent).

Agents of psittacosis and ornithosis.

Agents of lymphogranuloma venereum and granuloma inguinale.

The spirochetal agent of relapsing fever ( Borrelia recurrentis ).

The following gram-negative microorganisms:

Haemophilus ducreyi chancroid

Yersinia pestis and Francisella tularensis, formerly

Pasteurella pestis and Pasteurella tularensis,

Bartonella bacilliformis ,

Bacteroides species

Vibrio comma and Vibrio fetus,

Brucella species (in conjunction with streptomycin).

Because many strains of the following groups of microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are recommended.

ACHROMYCIN is indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:

Escherichia coli ,

Enterobacter aerogenes (formerly Aerobacter aerogenes ),

Shigella species

Mima species and Herellea species

Haemophilus influenzae (respiratory infections),

Klebsiella species (respiratory and urinary infections).

ACHROMYCIN is indicated for treatment of infections caused by the following gram-positive microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:

Streptococcus species:

Up to 44% of strains of Streptococcus pyogenes and 74% of Streptococcus faecalis have been found to be resistant to tetracycline drugs. Therefore, tetracyclines should not be used for streptococcal disease unless the organism has been demonstrated to be sensitive.

For upper respiratory infections due to Group A beta-hemolytic streptococci, penicillin is the usual drug of choice, including prophylaxis of rheumatic fever.

Streptococcus pneumoniae ,

Staphylococcus aureus, skin and soft tissue infections.

Tetracyclines are not the drug of choice in the treatment of any type of staphylococcal infection.

When penicillin is contraindicated, tetracyclines are alternative drugs in the treatment of infections due to:

Neisseria gonorrhoeae ,

Treponema pallidum  and Treponema pertenue   (syphilis and yaws),

Listeria monocytogenes ,

Clostridium  species,

Bacillus anthracis ,

Fusobacterium fusiforme   (Vincent's infection),

Actinomyces  species.

In acute intestinal amebiasis, the tetracyclines may be a useful adjunct to amebicides.

In severe acne, the tetracyclines may be useful adjunctive therapy.

ACHROMYCIN V is indicated in the treatment of trachoma, although the infectious agent is not always eliminated, as judged by immunofluorescence.

Inclusion conjunctivitis may be treated with oral tetracyclines or with a combination of oral and topical agents.

ACHROMYCIN is indicated for the treatment of uncomplicated urethral, endocervical or rectal infections in adults caused by Chlamydia trachomatis. 1

CONTRAINDICATIONS

This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.

THE USE OF DRUGS OF THE TETRACYCLINE CLASS DURING TOOTH DEVELOPMENT (LAST HALF OF PREGNANCY, INFANCY AND CHILDHOOD TO THE AGE OF 8 YEARS) MAY CAUSE PERMANENT DISCOLORATION OF THE TEETH (YELLOW-GRAY-BROWN). This adverse reaction is more common during long-term use of the drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. TETRACYCLINE DRUGS, THEREFORE, SHOULD NOT BE USED IN THIS AGE GROUP UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED.

If renal impairment exists, even usual oral or parenteral doses may lead to excessive systemic accumulation of the drug and possible liver toxicity. Under such conditions, lower than usual total doses are indicated and, if therapy is prolonged, serum level determinations of the drug may be advisable.

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema.

The anti-anabolic action of the tetracyclines may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired function, higher serum levels of tetracycline may lead to azotemia, hyperphosphatemia, and acidosis.

Usage in Pregnancy   (See above about use during tooth development.) Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity has also been noted in animals treated early in pregnancy.

Usage in Newborns, Infants, and Children   (See above about use during tooth development.)

All tetracyclines form a stable calcium complex in any bone forming tissue. A decrease in the fibula growth rate has been observed in prematures given oral tetracycline in doses of 25 mg/kg every six hours. This reaction was shown to be reversible when the drug was discontinued.

Tetracyclines are present in the milk of lactating women who are taking a drug in this class.

PRECAUTIONS

General

Pseudotumor cerebri (benign intracranial hypertension) in adults has been associated with the use of tetracyclines. The usual clinical manifestations are headache and blurred vision. Bulging fontanels have been associated with the use of tetracyclines in infants. While both of these conditions and related symptoms usually resolve soon after discontinuation of the tetracycline, the possibility for permanent sequelae exists.

As with other antibiotics preparations, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, the antibiotic should be discontinued and appropriate therapy should be instituted.

In venereal diseases when coexistent syphilis is suspected, darkfield examination should be done before treatment is started and the blood serology repeated monthly for at least 4 months.

In long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal and hepatic studies should be performed.

All infections due to Group A beta-hemolytic streptococci should be treated for at least ten days.

Drug Interactions

Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.

Since bacteriostatic drugs, such as the tetracycline class of antibiotics, may interfere with the bactericidal action of penicillins, it is not advisable to administer these drugs concomitantly.

Concurrent use of tetracyclines with oral contraceptives may render oral contraceptives less effective. Breakthrough bleeding has been reported.

ADVERSE REACTIONS

Gastrointestinal: nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, pancreatitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region, increases in liver enzymes, and hepatic toxicity have been reported rarely. Rare instances of esophagitis and esophageal ulcerations have been reported in patients taking the tetracycline-class antibiotics in capsule and tablet form. Most of these patients took the medication immediately before going to bed (see DOSAGE AND ADMINISTRATION ).

Skin: and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Fixed drug eruptions, including balanitis, have been rarely reported. Photosensitivity is discussed above. (See . )

Renal toxicity: in BUN has been reported and is apparently dose related. (See . )

Hypersensitivity reactions:  Urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, pericarditis and exacerbation of systemic lupus erythematosus.

Blood: anemia, thrombocytopenia, neutropenia and eosinophilia have been reported.

CNS:  Pseudotumor cerebri (benign intracranial hypertension) in adults and bulging fontanels in infants. (See PRECAUTIONS --General .) Dizziness, tinnitus, and visual disturbances have been reported. Myasthenic syndrome has been reported rarely.

Other:  When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid function studies are known to occur.

DOSAGE AND ADMINISTRATION

Therapy should be continued for at least 24 to 48 hours after symptoms and fever have subsided.

Concomitant therapy: containing aluminum, calcium, or magnesium impair absorption and should not be given to patients taking oral tetracycline.

Foods and some dairy products also interfere with absorption. Oral forms of tetracycline should be given 1 hour before or 2 hours after meals.

In patients with renal impairment: (See ). Total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses.

In the treatment of streptococcal infections, a therapeutic dose of tetracycline should be administered for at least ten days.

Adults:  Usual daily dose, 1-2 grams divided in two or four equal doses, depending on the severity of the infection.

For children above eight years of age:  Usual daily dose, 10-20 mg (25-50 mg/kg) per pound of body weight divided in two or four equal doses.

For treatment of brucellosis, 500 mg tetracycline four times daily for 3 weeks should be accompanied by streptomycin, 1 gram intramuscularly twice daily the first week and once daily the second week.

For treatment of syphilis, a total of 30-40 grams in equally divided doses over a period of 10-15 days should be given. Close follow up, including laboratory tests, is recommended.

Gonorrhea patients sensitive to pencillin may be treated with tetracycline, administered as an initial oral dose of 1.5 grams followed by 0.5 gram every 6 hours for four days to a total dosage of 9 grams.

Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis:   500 mg, by mouth, 4 times a day for at least 7 days. 1

HOW SUPPLIED

ACHROMYCIN® V tetracycline HCl oral dosage forms are available as follows:

CAPSULES

500 mg - Two-piece, hard shell, elongated, opaque capsules with a blue cap and a yellow body, printed with Lederle over A5 on one half and Lederle over 500 mg on the other in gray ink, supplied as follows:

NDC 0005-4875-23--Bottle of 100

NDC 0005-4875-34--Bottle of 1,000

250 mg - Two-piece, hard shell, opaque capsules with a blue cap and a yellow body, printed with Lederle over A3 on one half and Lederle over 250 mg on the other in gray ink, supplied as follows:

NDC 0005-4880-23--Bottle of 100

NDC 0005-4880-34--Bottle of 1,000

Store at Controlled Room Temperature 15°-30°C (59°-86°F).

Reference:  1. CDC Sexually Transmitted Diseases Treatment Guidelines 1982.

Manufactured by:

LEDERLE PHARMACEUTICAL DIVISION

American Cyanamid Company

Pearl River, NY 10965

CI 4945-1    Issued September 12, 1997